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The accepted definition of virtual histology intravascular ultrasound (IVUS-VH) thin-cap fibroatheroma (TCFA) is only a modest predictor of plaque rupture (PR). We sought to determine the relation between IVUS-VH findings and culprit lesions with PR using computational analysis. A total of 80 culprit lesions from 80 patients with stable angina (n = 37), unstable angina (n = 20), and myocardial infarction (n = 23) were divided into those with (n = 15) and without PR (n = 65). By use of automated computational analysis, the standard IVUS-VH TCFA criterion and 124 additional criteria were compared. The standard TCFA definition demonstrated modest ability to discriminate lesions with and without PR (sensitivity 87%, specificity 37%, PPV 0.24, and NPV 0.92). Of 124 additional IVUS-VH TCFA definitions, only 2 improved the discriminative ability even modestly. However, a positive correlation was demonstrated between cavity size and necrotic core percentage (r = 0.78, p <0.01) and a negative correlation with percentage of fibrous tissue (r = −0.81, p <0.01). In conclusion, IVUS-VH criteria were only modestly associated with PR, without significant improvement by varying IVUS-VH TCFA features, but IVUS-VH features of ruptured plaques were strongly correlated with cavity size.

Coronary artery disease is a leading cause of death in the Western world. Symptoms present only late in the progression of the disease, limiting treatment options; moreover, the inability to biopsy arterial tissue in a living patient makes it difficult to study the pathology effectively. 89 patients were imaged twice at a one year interval using x-ray angiography (the traditional modality for assessment of arterial stenosis) and intravascular ultrasound (IVUS), which yields a detailed image of the structure of the vessel wall. 32 of these 89 patients were made available for analysis in this study. The Volcano Corp. IVUS acquisition systems include software that provides a virtual histology (VH) characterization of plaque composition that provides information otherwise only available by biopsy. Using a geometric reconstruction method described in previous work, a full working model of wall shear stresses (WSS) produced by blood flow and vessel wall composition is created. Using these, the morphologic structural information gleaned from the 3-D reconstruction, and some additional composite indices, combined with demographic information collected at enrollment and serum biomarkers collected from each patient during imaging, a detailed portrait of each patient's disease state is created, with the objective of predicting disease evolution over a 1 year timescale. We have, in the course of this study, accomplished the following 5 aims towards the goal of predicting localized changes in disease state on a 1 year timescale: Aim 1: Develop and validate a method of compensating for rotational motion of the catheter within the vessel and its effect upon the 3-D orientation of the reconstruction. Aim 2: Develop and validate a method of registering the reconstructed vessels that permits identification of a point-to-point correspondence on all quantitative indices. Aim 3: Successfully reconstruct, register, and analyze image sets for each of as many patients as possible for analysis. Aim 4: Identify statistically significant indices in the data suitable for use as features in a classifier. Aim 5: Construct and assess performance of a classification system that can draw useful conclusions about the 1-year progression of the arterial pathology in a patient not used in the training set. Aim 2 was a complete success. Branches were reliably present in the IVUS data in sufficient quantities to facilitate reliable identification of the overlap and the requisite spatial transformation required to map points from one pullback onto another. Aim 1 was much more problematic. While a method was developed which showed promise, the image acquisition protocol did not provide for orientation of the angiograms with an eye towards bifurcation identification. With neither an analytic model, nor reasonable fiducials, the method developed could only be tested on a small subset of the data, limiting both our confidence in its validation, as well as its usability in this study. It is hoped that the method can be refined and used in any subsequent study, given proper planning during the acquisition of the images, and that in turn the spatial reliability of the reconstructions can be improved beyond what is possible today. Regarding aim 3, 32 patients were ultimately processed completely. Aims 4 and 5 were completed successfully. Meaningful correlations were identified in the data, and the results illustrate that while we were by no means able to obtain perfect classification, we were able to handily beat a both a random, and a maximum likelihood classifier.

A survey is performed of various Multi-Armed Bandit (MAB) strategies in order to examine their performance in circumstances exhibiting non-stationary stochastic reward functions in conjunction with delayed feedback. We run several MAB simulations to simulate an online eCommerce platform for grocery pick up, optimizing for product availability. In this work, we evaluate several popular MAB strategies, such as \\(\\epsilon\\)-greedy, UCB1, and Thompson Sampling. We compare the respective performances of each MAB strategy in the context of regret minimization. We run the analysis in the scenario where the reward function is non-stationary. Furthermore, the process experiences delayed feedback, where the reward function is not immediately responsive to the arm played. We devise a new adaptive technique (AG1) tailored for non-stationary reward functions in the delayed feedback scenario. The results of the simulation show show superior performance in the context of regret minimization compared to traditional MAB strategies.

Leadership is widely seen as having an important role in fostering ethical conduct in organizations, but the ways in which the actions of leaders intersect with formal ethics regulation in shaping conduct have been little researched. This article examines this issue through a qualitative study of the operation of the \"ethical framework\" for English local government, which entailed all councils adopting a code of conduct to regulate the behavior of local politicians. Studying local government provides an opportunity to examine how personal and managerial factors combine to influence ethical conduct and to analyze the ways in which ethical leadership is exercised through multiple people in leadership roles (politicians and managers). The article finds that organizations that exhibit consistently good conduct have multiple leaders who demonstrate good conduct but also act to preempt the escalation of problems and thereby minimize the explicit use of ethics regulation.

Concern for fostering trust in public institutions has prompted many governments to invest in systems of ethics regulation, embracing various dimensions of good governance. This article assesses the impact of ethics regulation on the conduct of English local politicians using Foucauldian perspectives on government, power, and resistance. The research finds that ethics regulation encountered problems when politicians resisted the models of political identity and behavior that it was perceived to promote. Particular concentrations of misconduct complaints were identified in which politicians believed that changes to political management structures, designed to make local governance more effective, caused a loss of voice for elected representatives. Ethics regulation itself sometimes served as a device for controlling others and effecting resistance. The article concludes with reflections on how far we should expect political conduct to be managed by such regulatory practices.

Background The World Health Organization (WHO) published the WHO Labour Care Guide (LCG) in 2020 to support the implementation of its 2018 recommendations on intrapartum care. The WHO LCG promotes evidence-based labour monitoring and stimulates shared decision-making between maternity care providers and labouring women. There is a need to identify critical questions that will contribute to defining the research agenda relating to implementation of the WHO LCG. Methods This mixed-methods prioritization exercise, adapted from the Child Health and Nutrition Research Initiative (CHNRI) and James Lind Alliance (JLA) methods, combined a metrics-based design with a qualitative, consensus-building consultation in three phases. The exercise followed the reporting guideline for priority setting of health research (REPRISE). First, 30 stakeholders were invited to submit online ideas or questions (generation of research ideas). Then, 220 stakeholders were invited to score \"research avenues\" (i.e., broad research ideas that could be answered through a set of research questions) against six independent and equally weighted criteria (scoring of research avenues). Finally, a technical working group (TWG) of 20 purposively selected stakeholders reviewed the scoring, and refined and ranked the research avenues (consensus-building meeting). Results Initially, 24 stakeholders submitted 89 research ideas or questions. A list of 10 consolidated research avenues was scored by 75/220 stakeholders. During the virtual consensus-building meeting, research avenues were refined, and the top three priorities agreed upon were: (1) optimize implementation strategies of WHO LCG, (2) improve understanding of the effect of WHO LCG on maternal and perinatal outcomes, and the process and experience of labour and childbirth care, and (3) assess the effect of the WHO LCG in special situations or settings. Research avenues related to the organization of care and resource utilization ranked lowest during both the scoring and consensus-building process. Conclusion This systematic and transparent process should encourage researchers, program implementers, and funders to support research aligned with the identified priorities related to WHO LCG. An international collaborative platform is recommended to implement prioritized research by using harmonized research tools, establishing a repository of research priorities studies, and scaling-up successful research results.

Governments around the world are concerned about declining public confidence in democratic institutions. It has been widely assumed that improving the performance of public services will help address this problem. Policy makers in the United Kingdom (UK) have therefore been puzzled to discover that public confidence in local government continued to decline at a time when local services seemed to be improving. The reason for this apparent paradox is that public confidence is influenced by a wide array of factors only some of which are captured by official measures. Since different data can lead to quite different conclusions, it matters what is measured.

Death adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment. Definite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5-74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5-15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5-168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4-245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom. Death adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persistent neurological effects despite antivenom, suggests that neurotoxicity is not reversed by antivenom.

Government efforts to increase civic engagement are predicated, in part, on the belief that this will lead to better public services. This assumption is tested by analysing the impact of different approaches to supporting active citizenship in English local authorities on their recorded service performance in 2005. Performance and support for active citizenship are modelled using data drawn from a national survey and secondary sources. The results suggest that councils which aim to promote understanding of citizenship among the public are more likely to have higher service performance, but that those which aim to increase citizen engagement in local governance are associated with lower performance in deprived areas.